Pathogens are disease-causing organisms. By natural selection, they develop evading mechanisms to outsmart the host’s immune system and to get the upper hand. One way to support the immune system and fight back is medical intervention. However, this can lead to unwanted adaptions of pathogens as seen in antibiotic-resistant bacteria. Another strategy is social intervention. Some social groups like ants are trying to fight infection with “social immunity,” the collective hygiene and health care measures to avoid spreading throughout the community. If and how pathogens can respond to this kind of group behavior, is still unknown.

The latest study by Professor Sylvia Cremer and her research team at the Institute of Science and Technology Austria (ISTA) shows the extraordinary effects of these kinds of host-parasite interactions. Together, with chemical ecologists at the University of Würzburg in Germany, the scientists took a close look at social ants, to see how pathogenic fungi respond to their hosts’ social care intervention during infection. The results reveal that fungi reduce their chemical detection signals to outplay social immunity. The study is published today in Nature Ecology & Evolution.

More spores but less grooming

“Fungi infect the ants from the body surface and grow inside, but nestmates groom off many of the spores before they can even cause internal infection,” explains Barbara Milutinović, one of the lead authors, former postdoc in the Cremer Group and now Marie Curie Sklodowska Fellow at Ruđer Bošković Institute in Croatia. The scientists set up an experiment where Argentine ants (Linepithemahumile) were infected with pathogenic Metarhizium fungi either in the absence or presence of caregiving colony members. “We found that the fungi fundamentally changed in response to the ant workers’ caregiving,” Milutinović continues. Over ten infection cycles, fungi which experienced grooming nestmate ants boosted their spore production compared to fungi accompanied by only individual ants. “Producing more spores will help the fungus counteract the spore-removal by helping nestmates. Yet, we were surprised to see that the ants showed less grooming against the spores,” Sylvia Cremer adds. “This suggests, that the spores have become more difficult to detect by the ants.”

Fungi lose their typical chemical profile

To check why ant workers had difficulties sensing fungi and to analyze possible fungal detection cues, the scientists teamed up with a chemical ecologist from the University of Würzburg. Local Professor Thomas Schmitt explains: “The fungi, that adapted to social hosts were perceived less strongly, due to a strong reduction of a fungi-specific compound called ergosterol.” Ergosterol is an essential membrane compound, that all fungi have. By exposing the ants to pure fungal ergosterol or the slightly different non-fungal vertebrate equivalent, the researchers showed, that only the fungal compound induced intense grooming. Milutinović summarizes: “This demonstrates that fungal pathogens react to the presence of caregiving ants by reducing their characteristic fungal signals. They are no longer recognized as a disease threat and can escape the social immunity of the colony.”

The findings highlight the impact that social hosts have on their pathogens by group behaviors. “It’s fascinating how collective hygiene measures trigger evasion strategies in the pathogen. It would be interesting to see how the ant colony will react in turn. Maybe they become more sensitive in detecting lower and lower fungal cues,” Cremer concludes.

An ischemic stroke is caused by a blockage of blood flow to the brain and is the most common type of stroke. An intracerebral hemorrhage is caused by bleeding in the brain.

“Our study suggests that higher estrogen levels due to a number of reproductive factors, including a longer reproductive life span and using hormone therapy or contraceptives, are linked to a lower risk of ischemic stroke and intracerebral hemorrhage,” said study author Peige Song, PhD, of the Zhejiang University School of Medicine in Hangzhou, China. “These findings might help with new ideas for stroke prevention, such as considering screenings for people who have a short lifetime exposure to estrogen.”

The study involved 122,939 postmenopausal female participants with a median age of 58 living in China without stroke at the start of the study.

Participants answered questions on personal factors, such as age, sex, and occupation, as well as lifestyle factors, such as smoking, alcohol use, exercise and medical history. They also answered questions on reproductive health information, including age at first menstruation and start of menopause, number of pregnancies and miscarriages and oral contraceptive use.

Researchers looked at health insurance and disease registry data to determine which participants had a stroke. During an average follow-up period of nine years, 15,139 had a stroke. Of those,12,853 had ischemic stroke, 2,580 had intracerebral hemorrhage and 269 had subarachnoid hemorrhage, which is bleeding between the brain and the membrane that covers it.

Participants were divided into four groups determined by their reproductive life span, the number of years from first menstruation to menopause. Participants in the group with the shortest reproductive life span had up to 31 reproductive years. Participants in the group with the longest reproductive lifespan had 36 reproductive years or more.

As a percentage, participants in the longest group had slightly more strokes than those in the shortest group, 13.2% compared to 12.6%. But when researchers adjusted for other factors that could affect stroke risk, such as age, smoking, physical activity and high blood pressure, they found that participants in the longest group had a 5% lower risk of all kinds of stroke.

When looking at different types of stroke, female participants with the longest reproductive life span had a 5% lower risk of ischemic stroke and a 13% lower risk of intracerebral hemorrhage when compared to women with the shortest reproductive life span.

Researchers also looked at other factors affecting estrogen levels, such as number of births and use of oral contraceptives, both of which are associated with higher levels, and length of breastfeeding, which is associated with lower levels based on the hypothesis that pregnancy and oral contraceptive use represent relatively higher sustained blood estrogen levels. They found that higher estrogen levels led to a lower risk of all types of stroke, as well as ischemic stroke and intracerebral hemorrhage.

“Estrogen exposure throughout life could potentially be a useful indicator of a person’s risk of different types of stroke following menopause,” said Song. “However, more research is needed on the biological, behavioral, and social factors that may contribute to the link between estrogen exposure and stroke risk across a woman’s lifespan.”

A limitation of the study was that information on reproductive factors was collected mainly based on participants’ ability to recall events, and participants may not have remembered such events correctly.

Multiple sclerosis is an autoimmune disease in which the myelin, or fatty lining of nerve cells, is eroded, leading to nerve damage and slower signalling between the brain and the body. MS symptoms range from blurred vision to complete paralysis, and while there are treatments, the causes are not fully understood and nothing exists to reverse the disease process. More than 90,000 Canadians live with MS, according to the MS Society.

In new research published in Stem Cell Reports, Anastassia Voronova, an assistant professor and Canada Research Chair in Neural Stem Cell Biology, injected fractalkine into mice with chemically induced MS.

She found the treatment increased the number of new oligodendrocytes — vital brain and spinal cord cells that produce myelin in both embryonic and adult brains — which are damaged during the MS autoimmune attack.

“If we can replace those lost or damaged oligodendrocytes, then they could make new myelin and it is believed that would halt the disease progression, or maybe even reverse some of the symptoms,” Voronova says. “That’s the Holy Grail in the research community and something that we’re very passionate about.”

Voronova’s earlier research tested the safety and efficacy of fractalkine in normal mice and found similar beneficial effects. Other researchers have demonstrated that fractalkine may provide protection for nerves in mouse models before the disease is induced, but this is the first time it has been tested on animals that already have the disease.

Voronova and her team observed new oligodendrocytes, as well as reactivated progenitor cells that can regenerate oligodendrocytes, in the brains of the treated animals. Remyelination occurred in both the white and grey matter. The researchers also observed a reduction in inflammation, part of the damage caused by the immune system. Next steps for the treatment include testing it in other diseased mouse models, including those with neurodegenerative diseases other than MS.

The study, begun in 2001 and published this month in the Journal of the American College of Cardiology, analyzed brain imaging data from 270 full-term UCSF and BCCH newborns with congenital heart disease (CHD) for changes in brain injuries before and after newborn cardiac surgery. The scientists confirmed that recent advances in surgical and clinical care that maintain a higher postoperative blood pressure resulted in reducing brain injuries and better chances of patient survival.

“We were surprised to find that advances in care over the past 7 years resulted in a clear decline in brain injury linked to increasing the patient’s blood pressure following surgery,” said Shabnam Peyvandi, MD, lead author and pediatric cardiologist for UCSF Benioff Children’s Hospitals. “With advances in cardiac therapy and outcomes, our focus now is helping these children thrive.”

CHD, which refers to one or more abnormalities of an infant’s heart, impacts 40,000 newborns a year in the U.S. It is the most common newborn birth defect. About 1 in 4 of these infants have critical CHD and require surgery in the first month to first year of life. Heart abnormalities include improperly functioning heart valves, a hole in the muscular wall separating the heart chambers, and malformations in the heart’s blood vessels, which can result in altered patterns of blood flow. These anomalies reduce the flow of oxygen and nutrients to the brain and organs before birth, and can contribute to lifelong neurological and developmental disorders.

New Approaches to Monitor Brain Health

To monitor infant brain health for the study, UCSF and BCCH scientists used advanced magnetic resonance (MRI) brain imaging before and after heart surgery and consistently as the patient aged. The data was divided into four sequential stages, each containing five consecutive years of data. In the fourth and final stage, which ran from 2016 to 2021, infants were maintained at higher post-surgical blood pressures than in previous groups. This resulted in an almost 20% reduction in post-surgical brain injuries compared to the first group in 2001.

During the course of this study, Peyvandi and the UCSF Benioff Children’s Hospitals Pediatric Heart Center published multiple articles investigating brain development and white matter injuries — including a link between moderate-severe white matter injuries that led to delays in childhood motor function — that opened the door to improving long term developmental outcomes by decreasing early brain injuries.

“Taken together, these findings underscore the importance of tracking brain injury and implementing changes to reduce occurrences that will improve outcomes,” said Patrick McQuillen, MD, senior author and professor of Pediatrics, UCSF Benioff Children’s Hospitals. “Based on this research and others, several leading heart centers have incorporated brain imaging into routine clinical practice.”

Work from this group has directly informed the creation of novel clinical programs to monitor and protect the brain in fetuses, newborns and children with CHD, including the Healthy Hearts & Minds Program and the Neonatal Cardiovascular Center of Excellence Growth and Neurodevelopment (GRAND) program that incorporates developmental care on the inpatient setting for newborns with critical CHD.

Other UCSF authors include Duan Xu, PHD, A. James Barkovich, MD, Dawn Gano, MD, MAS, V. Mohan Reddy, MD

The researchers hope to turn this discovery into viable treatment for some types of antibiotic-resistant infections. Antibiotic-resistant infections kill more than a million people globally each year.

For centuries, silver has been known to have antimicrobial properties. However, silver nanoparticles — microscopic spheres of silver small enough to operate at the cellular level — represent a new frontier in using the precious metal to fight bacteria.

In this study, the research team tested whether commercially available silver nanoparticles boost the power of antibiotics and enable these drugs to counter the very bacteria that have evolved to withstand them.

“We found that the silver nanoparticles and a common class of broad-spectrum antibiotics called aminoglycosides work together synergistically,” said Daniel Czyż, senior author of the study and an assistant professor in the UF/IFAS department of microbiology and cell science.

“When combined with a small amount of silver nanoparticles, the amount of antibiotic needed to inhibit the bacteria decreased 22-fold, which tells us that the nanoparticles make the drug much more potent,” Czyż explained. “In addition, aminoglycosides can have negative side effects, so using silver nanoparticles could allow for a lower dose of antibiotic, reducing those side effects.”

The findings were both surprising and exciting, said Autumn Dove, first author of the study and a doctoral candidate studying microbiology and cell science in the UF/IFAS College of Agricultural and Life Sciences.

“When I first saw the result, my first thoughts were, ‘Wow, this works!'” said Dove.

Over the last several decades, overuse of antibiotics had led to the emergence of antibiotic-resistant bacteria and a decline in the effectiveness of traditional antibiotic drugs, the researchers said. The study’s findings indicate that silver nanoparticles have the potential to renew the effectiveness of some of these drugs.

“Let’s say you get a bad burn on your hand, and it gets infected with one of these resistant strains of bacteria,” Dove said. “It’s possible that dressing that burn with a combination of silver nanoparticles and antibiotics could both clear that infection and prevent those resistant bacteria from spreading elsewhere.”

Though antibiotics mainly target bacteria, they can also damage human and animal cells. Using a microscopic worm called C. elegans, the researchers confirmed that the silver nanoparticles did not also make the antibiotic more toxic to non-bacterial cells.

Building off the study’s promising findings, the scientists next plan to seek FDA authorization for clinical trials and work with UF Innovate to patent an antimicrobial product that uses silver nanoparticles.

The silver nanoparticles used in the study were manufactured by the Natural Immunogenics Corporation, which helped fund the study through the UF Industry Partnerships Matching Grant Program. This program pairs UF researchers with Florida-based technology and energy companies to research and develop new products.